ORIGINAL ARTICLE pISSN 2288-6575 • eISSN 2288-6796 http://dx.doi.org/10.4174/astr.2014.86.3.115 Annals of Surgical Treatment and Research
The pattern and significance of the calcifications of papillary thyroid microcarcinoma presented in preoperative neck ultrasonography Eun Mee Oh, Yoo Seung Chung, Won Jong Song, Young Don Lee Department of Thyroid and Endocrine Surgery, Gachon University Gil Medical Center, Incheon, Korea
Purpose: To analyze the incidence and patterns of calcification of papillary thyroid microcarcinoma (PTMC) on neck ultrasonography (NUS) and assess the clinical implications of calcification, especially for neck node metastasis. Methods: The clinical data of 379 patients with PTMC who underwent thyroidectomy between January and December 2011 were retrospectively analyzed. PTMC lesions were classified into four subgroups according to their calcification patterns on preoperative NUS: microcalcification, macrocalcification, rim calcification, and noncalcification. The clinicopathologic characteristics were compared between the patients with and without calcification, and among the four subgroups. Results: Calcifications were detected on NUS in 203 patients (53.5%) and central neck node metastasis was observed in 119 patients (31.3%). Calcification was associated with larger tumor size (0.68 cm vs. 0.54 cm), higher rate of lymph node metastasis (38.6% vs. 23.2%) and higher lymph node ratio (0.11 vs. 0.06) compared to noncalcification (All P < 0.05). In addition, the extent of calcification correlated with lesion size (0.67 cm vs. 0.69 cm vs. 0.85 cm). Further, the likelihood of lymph node metastasis also correlated with the extent of calcification in the order of non-, micro- and macrocalcification (23.3%, 36.8%, and 44.1%, respectively). The calcification rate was higher in patients with lymph node metastasis than those without it (65.5% vs. 47.7%) (All P < 0.05). Conclusion: PTMC patients positive for calcification on NUS had a higher rate of lymph node metastasis, and a higher lymph node ratio compared to noncalcification patients. Calcification patterns should be assessed carefully in patients with PTMC by preoperative NUS. [Ann Surg Treat Res 2014;86(3):115-121] Key Words: Papillary thyroid microcarcinoma, Calcification, Ultrasonography
INTRODUCTION The prevalence of papillary thyroid microcarcinoma (PTMC) has increased recently, due in part to the increased use of neck ultrasonography (NUS) and NUS-guided fine needle aspiration cytology [1]. NUS features that suggest malignancy in a thyroid nodule include microcalcifications, the absence of “halo” sign, marked hypoechogenicity, extrathyroidal extension, an irregular or microlobulated margin, and a heterogeneous echo structure
Received July 24, 2013, Revised December 24, 2013, Accepted December 30, 2013 Corresponding Author: Young Don Lee Department of Thyroid and Endocrine Surgery, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 405-760, Korea Tel: +82-32-460-8419, Fax: +82-32-461-3214 E-mail: [email protected]
[2]. Calcifications on thyroid ultrasonography can be classified as micro- or macrocalcifications, and microcalcification considered to be the most specific sonographic indicator in the diagnosis of papillary thyroid carcinoma (PTC) [3]. PTCs are the most common type of thyroid cancer, often forming concentric calcified foci, called psammoma bodies, which are strongly diagnostic for PTC [4]. On NUS, psammoma bodies appear as fine, scattered, and punctate bright echoes, indicative of microcalcifications. Other types of calcification,
Copyright ⓒ 2014, the Korean Surgical Society cc Annals of Surgical Treatment and Research is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution NonCommercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Annals of Surgical Treatment and Research
115
Annals of Surgical Treatment and Research 2014;86(3):115-121
including coarse, macro, eggshell and rim calcifications, were formerly thought to be more common in benign thyroid tumors than in malignant thyroid tumors. However, these patterns have also been observed in malignant lesions, although microcalcifications remain the most frequent type in thyroid malignancies [5]. The mechanism of formation of microcalcifications in PTC was thought to involve a poor blood supply to the nipple, leading to calcification necrosis [6]. More recently, however, osteopontin (OPN) became known as the cause of formation of microcalcifications [7]. Moreover, OPN expression was found to be significantly related to lymph node metastasis [8,9]. Thus, to date, the molecular mechanism responsible for calcification in PTC has not been determined, nor has the clinical significance of calcification in thyroid malignancy, including PTMCs. This study was therefore designed to analyze the incidence and patterns of PTMC calcification on NUS and to assess the clinical implications of PTMC calcification.
METHODS The NUS findings and clinical data of 379 patients with PTMC who underwent thyroidectomy between January and December 2011 were retrospectively reviewed. All preoperative NUS examinations were performed by one endocrine surgeon and several thyroid radiologists at Gachon University Gil Medical Center. Electronic patient records were reviewed, and NUS findings were reviewed and analyzed in detail by a single endocrine surgeon, who paid close attention to the presence and patterns of calcifications. PTMC calcifications were classified by size and pattern as, namely, microcalcification (defined as punctate echogenic foci ≤1 mm with or without posterior shadowing), macro calcifications (defined as punctate echogenic foci >1 mm in size), or rim calcifications (defined as nodules with peripheral curvilinear or eggshell calcifications) [10]. Of the 379 patients, 136 (35.9%) had microcalcifications, 59 (15.6%)
Fig. 1. Papillary thyroid microcarcinoma calcification patterns on neck neck ultrasonography. (A) Noncalcification: taller than wide, ill-defined hypoechoic nodule. (B) Microcalcification: several calcifications measuring less than 1 mm. (C) Macrocalcification: one calcification larger than 1 mm. (D) Rim calcification: ring-shaped calcification on the periphery of the nodule.
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had macrocalcification, 8 (2.1%) had rim calcifications, and remaining 176 patients (46.4%) did not have any calcifications (Fig. 1). A total thyroidectomy with bilateral central neck compar tment dissection was performed on 198 of the 379 patients, and 181 underwent unilateral lobectomy including the isthmus with unilateral central neck node dissection. Moreover, 56 patients (14.7%) who had suspicious lymph node enlargement on NUS underwent therapeutic central lymph node dissection (CND), with the remaining 323 (85.2%) undergoing prophylactic CND. The study protocol was approved by our Institutional Review Board, which waived the requirement for informed consent due to the retrospective nature of this study. The chi-square and independent t-tests were used to com pare clinicopathologic data between the 203 patients with calcification and the 176 without calcification. Data in the four patient subgroups were compared using the analysis of variance and Kruskal-Wallis H test. All statistical analyses were performed using the IBM SPSS ver. 19.0 (IBM Co., Armonk, NY, USA). A P-value of
The pattern and significance of the calcifications of papillary thyroid microcarcinoma presented in preoperative neck ultrasonography Eun Mee Oh, Yoo Seung Chung, Won Jong Song, Young Don Lee Department of Thyroid and Endocrine Surgery, Gachon University Gil Medical Center, Incheon, Korea
Purpose: To analyze the incidence and patterns of calcification of papillary thyroid microcarcinoma (PTMC) on neck ultrasonography (NUS) and assess the clinical implications of calcification, especially for neck node metastasis. Methods: The clinical data of 379 patients with PTMC who underwent thyroidectomy between January and December 2011 were retrospectively analyzed. PTMC lesions were classified into four subgroups according to their calcification patterns on preoperative NUS: microcalcification, macrocalcification, rim calcification, and noncalcification. The clinicopathologic characteristics were compared between the patients with and without calcification, and among the four subgroups. Results: Calcifications were detected on NUS in 203 patients (53.5%) and central neck node metastasis was observed in 119 patients (31.3%). Calcification was associated with larger tumor size (0.68 cm vs. 0.54 cm), higher rate of lymph node metastasis (38.6% vs. 23.2%) and higher lymph node ratio (0.11 vs. 0.06) compared to noncalcification (All P < 0.05). In addition, the extent of calcification correlated with lesion size (0.67 cm vs. 0.69 cm vs. 0.85 cm). Further, the likelihood of lymph node metastasis also correlated with the extent of calcification in the order of non-, micro- and macrocalcification (23.3%, 36.8%, and 44.1%, respectively). The calcification rate was higher in patients with lymph node metastasis than those without it (65.5% vs. 47.7%) (All P < 0.05). Conclusion: PTMC patients positive for calcification on NUS had a higher rate of lymph node metastasis, and a higher lymph node ratio compared to noncalcification patients. Calcification patterns should be assessed carefully in patients with PTMC by preoperative NUS. [Ann Surg Treat Res 2014;86(3):115-121] Key Words: Papillary thyroid microcarcinoma, Calcification, Ultrasonography
INTRODUCTION The prevalence of papillary thyroid microcarcinoma (PTMC) has increased recently, due in part to the increased use of neck ultrasonography (NUS) and NUS-guided fine needle aspiration cytology [1]. NUS features that suggest malignancy in a thyroid nodule include microcalcifications, the absence of “halo” sign, marked hypoechogenicity, extrathyroidal extension, an irregular or microlobulated margin, and a heterogeneous echo structure
Received July 24, 2013, Revised December 24, 2013, Accepted December 30, 2013 Corresponding Author: Young Don Lee Department of Thyroid and Endocrine Surgery, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 405-760, Korea Tel: +82-32-460-8419, Fax: +82-32-461-3214 E-mail: [email protected]
[2]. Calcifications on thyroid ultrasonography can be classified as micro- or macrocalcifications, and microcalcification considered to be the most specific sonographic indicator in the diagnosis of papillary thyroid carcinoma (PTC) [3]. PTCs are the most common type of thyroid cancer, often forming concentric calcified foci, called psammoma bodies, which are strongly diagnostic for PTC [4]. On NUS, psammoma bodies appear as fine, scattered, and punctate bright echoes, indicative of microcalcifications. Other types of calcification,
Copyright ⓒ 2014, the Korean Surgical Society cc Annals of Surgical Treatment and Research is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution NonCommercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Annals of Surgical Treatment and Research
115
Annals of Surgical Treatment and Research 2014;86(3):115-121
including coarse, macro, eggshell and rim calcifications, were formerly thought to be more common in benign thyroid tumors than in malignant thyroid tumors. However, these patterns have also been observed in malignant lesions, although microcalcifications remain the most frequent type in thyroid malignancies [5]. The mechanism of formation of microcalcifications in PTC was thought to involve a poor blood supply to the nipple, leading to calcification necrosis [6]. More recently, however, osteopontin (OPN) became known as the cause of formation of microcalcifications [7]. Moreover, OPN expression was found to be significantly related to lymph node metastasis [8,9]. Thus, to date, the molecular mechanism responsible for calcification in PTC has not been determined, nor has the clinical significance of calcification in thyroid malignancy, including PTMCs. This study was therefore designed to analyze the incidence and patterns of PTMC calcification on NUS and to assess the clinical implications of PTMC calcification.
METHODS The NUS findings and clinical data of 379 patients with PTMC who underwent thyroidectomy between January and December 2011 were retrospectively reviewed. All preoperative NUS examinations were performed by one endocrine surgeon and several thyroid radiologists at Gachon University Gil Medical Center. Electronic patient records were reviewed, and NUS findings were reviewed and analyzed in detail by a single endocrine surgeon, who paid close attention to the presence and patterns of calcifications. PTMC calcifications were classified by size and pattern as, namely, microcalcification (defined as punctate echogenic foci ≤1 mm with or without posterior shadowing), macro calcifications (defined as punctate echogenic foci >1 mm in size), or rim calcifications (defined as nodules with peripheral curvilinear or eggshell calcifications) [10]. Of the 379 patients, 136 (35.9%) had microcalcifications, 59 (15.6%)
Fig. 1. Papillary thyroid microcarcinoma calcification patterns on neck neck ultrasonography. (A) Noncalcification: taller than wide, ill-defined hypoechoic nodule. (B) Microcalcification: several calcifications measuring less than 1 mm. (C) Macrocalcification: one calcification larger than 1 mm. (D) Rim calcification: ring-shaped calcification on the periphery of the nodule.
116
Eun Mee Oh, et al: Calcification of papillary microcarcinoma
had macrocalcification, 8 (2.1%) had rim calcifications, and remaining 176 patients (46.4%) did not have any calcifications (Fig. 1). A total thyroidectomy with bilateral central neck compar tment dissection was performed on 198 of the 379 patients, and 181 underwent unilateral lobectomy including the isthmus with unilateral central neck node dissection. Moreover, 56 patients (14.7%) who had suspicious lymph node enlargement on NUS underwent therapeutic central lymph node dissection (CND), with the remaining 323 (85.2%) undergoing prophylactic CND. The study protocol was approved by our Institutional Review Board, which waived the requirement for informed consent due to the retrospective nature of this study. The chi-square and independent t-tests were used to com pare clinicopathologic data between the 203 patients with calcification and the 176 without calcification. Data in the four patient subgroups were compared using the analysis of variance and Kruskal-Wallis H test. All statistical analyses were performed using the IBM SPSS ver. 19.0 (IBM Co., Armonk, NY, USA). A P-value of
